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Сравнительная оценка прогностической ценности самостоятельного и врачебного забора материала для ВПЧ-теста
Сравнительная оценка прогностической ценности самостоятельного и врачебного забора материала для ВПЧ-теста
Белокриницкая Т.Е., Туранова О.В., Фролова Н.И. Сравнительная оценка прогностической ценности самостоятельного и врачебного забора
материала для ВПЧ-теста. Гинекология. 2018; 20 (2): 51–54.
DOI: 10.26442/2079-5696_2018.2.51-54
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Аннотация
Цель исследования. Оценить прогностическую ценность самостоятельного и врачебного забора вагинального отделяемого для ВПЧ-теста.
Материалы и методы. В исследование вошли 200 женщин в возрасте 18–45 лет (средний возраст 32,7±6,9 года), которым было выполнено традиционное цитологическое исследование и тестирование на вирус папилломы человека (ВПЧ) высокого канцерогенного риска (ВКР). Забор вагинального секрета для идентификации ДНК ВПЧ методом полимеразной цепной реакции выполнялся самостоятельно женщиной с помощью прибора «Qvintip» и врачом – из цервикального канала. Прогностическая ценность этих методик оценивалась по общепринятым формулам.
Результаты. ВПЧ ВКР выявлен у 42% обследованных. Наиболее распространенными типами были ВПЧ-16 (17,7%), ВПЧ-56 (16,3%), ВПЧ-39 (13,6%). У 51,2% ВПЧ-положительных женщин отмечалось сочетание нескольких типов ВПЧ ВКР. Результативность обследования с помощью устройства «Qvintip» была выше, чем при заборе материала врачом: 38% vs 27,5% (отношение шансов – ОШ=1,6; 95% доверительный интервал – ДИ 0,48–2,45; χ2=5,0, pχ2=0,025). Устройство «Qvintip» выявляло ВПЧ ВКР в 5 раз чаще: 34,5% vs 9,5% (ОШ=5,0; 95% ДИ 1,61–6,71; χ2=15,3, pχ2=0,0001). Аномальная цитологическая картина выявлена только у ВПЧ-позитивных женщин в 17,9% (χ2=19,9, pχ2=0,0005), из них LSIL обнаружены в 15,5% случаев, HSIL – в 2,4%. Сравнительная оценка прогностической ценности выявила более высокую чувствительность метода самозабора (100%) по сравнению с врачебным забором материала (66,7%). Выявлена высокая специфичность обеих методик приготовления образцов для ВПЧ-теста: 65% – для самостоятельного и 72% – для врачебного.
Заключение. Устройство «Qvintip» для самостоятельного забора вагинального отделяемого для ВПЧ-теста обладает высокой прогностической ценностью и может быть рекомендовано в качестве альтернативного метода при скрининге рака шейки матки.
Ключевые слова: вирус папилломы человека высокого канцерогенного риска, ВПЧ-тест, шейка матки, самозабор, «Qvintip», прогностическая ценность.
Materials and methods. The study included 200 women aged 18–45 years (mean age 32.7±6.9 years) who underwent traditional cytological testing and testing for HPV-stimulated stimulation. The vaginal secretion for the identification of HPV DNA by polymerase chain reaction (PCR) was performed by a woman alone using a Qvintip device and a doctor from the cervical canal. The predictive value of these techniques was evaluated according to generally accepted formulas.
Results. 42% of those surveyed had HPV-stimulated stimulation. The most common types were HPV-16 (17.7%), HPV-56 (16.3%), HPV-39 (13.6%). 51.2% of HPV-positive women had a combination of several types of HPV-stimulated stimulation. The effectiveness of the examination with the Qvintip device was higher than when the doctor took the material: 38% vs 27.5% (OR=1.6, 95% CI 0.48–2.45, χ2=5.0, pχ2=0.025). The Qvintip device detected a 5-fold increase in HPV-SRV: 34.5% vs 9.5% (OR=5.0, 95% CI 1.61–6.71, χ2=15.3, pχ2=0.0001). An abnormal cytological picture was found only in HPV-positive women in 17.9% (χ2=19.9, pχ2=0.0005), of which LSIL were detected in 15.5% of cases, HSIL-2.4%. A comparative assessment of prognostic value revealed a higher sensitivity of the self-sampling method (100%) compared with the medical fence of the material (66.7%). High specificity of both methods of preparation of samples for HPV-test was revealed: 65% for independent and 72% for medical.
The conclusion. The Qvintip device for self-sampling vaginal discharge for the HPV test has a high predictive value and can be recommended as an alternative method for screening cervical cancer.
Key words: human papillomavirus high carcinogenic risk, HPV test, cervix, sampling, Qvintip, prognostic value.
Материалы и методы. В исследование вошли 200 женщин в возрасте 18–45 лет (средний возраст 32,7±6,9 года), которым было выполнено традиционное цитологическое исследование и тестирование на вирус папилломы человека (ВПЧ) высокого канцерогенного риска (ВКР). Забор вагинального секрета для идентификации ДНК ВПЧ методом полимеразной цепной реакции выполнялся самостоятельно женщиной с помощью прибора «Qvintip» и врачом – из цервикального канала. Прогностическая ценность этих методик оценивалась по общепринятым формулам.
Результаты. ВПЧ ВКР выявлен у 42% обследованных. Наиболее распространенными типами были ВПЧ-16 (17,7%), ВПЧ-56 (16,3%), ВПЧ-39 (13,6%). У 51,2% ВПЧ-положительных женщин отмечалось сочетание нескольких типов ВПЧ ВКР. Результативность обследования с помощью устройства «Qvintip» была выше, чем при заборе материала врачом: 38% vs 27,5% (отношение шансов – ОШ=1,6; 95% доверительный интервал – ДИ 0,48–2,45; χ2=5,0, pχ2=0,025). Устройство «Qvintip» выявляло ВПЧ ВКР в 5 раз чаще: 34,5% vs 9,5% (ОШ=5,0; 95% ДИ 1,61–6,71; χ2=15,3, pχ2=0,0001). Аномальная цитологическая картина выявлена только у ВПЧ-позитивных женщин в 17,9% (χ2=19,9, pχ2=0,0005), из них LSIL обнаружены в 15,5% случаев, HSIL – в 2,4%. Сравнительная оценка прогностической ценности выявила более высокую чувствительность метода самозабора (100%) по сравнению с врачебным забором материала (66,7%). Выявлена высокая специфичность обеих методик приготовления образцов для ВПЧ-теста: 65% – для самостоятельного и 72% – для врачебного.
Заключение. Устройство «Qvintip» для самостоятельного забора вагинального отделяемого для ВПЧ-теста обладает высокой прогностической ценностью и может быть рекомендовано в качестве альтернативного метода при скрининге рака шейки матки.
Ключевые слова: вирус папилломы человека высокого канцерогенного риска, ВПЧ-тест, шейка матки, самозабор, «Qvintip», прогностическая ценность.
________________________________________________
Materials and methods. The study included 200 women aged 18–45 years (mean age 32.7±6.9 years) who underwent traditional cytological testing and testing for HPV-stimulated stimulation. The vaginal secretion for the identification of HPV DNA by polymerase chain reaction (PCR) was performed by a woman alone using a Qvintip device and a doctor from the cervical canal. The predictive value of these techniques was evaluated according to generally accepted formulas.
Results. 42% of those surveyed had HPV-stimulated stimulation. The most common types were HPV-16 (17.7%), HPV-56 (16.3%), HPV-39 (13.6%). 51.2% of HPV-positive women had a combination of several types of HPV-stimulated stimulation. The effectiveness of the examination with the Qvintip device was higher than when the doctor took the material: 38% vs 27.5% (OR=1.6, 95% CI 0.48–2.45, χ2=5.0, pχ2=0.025). The Qvintip device detected a 5-fold increase in HPV-SRV: 34.5% vs 9.5% (OR=5.0, 95% CI 1.61–6.71, χ2=15.3, pχ2=0.0001). An abnormal cytological picture was found only in HPV-positive women in 17.9% (χ2=19.9, pχ2=0.0005), of which LSIL were detected in 15.5% of cases, HSIL-2.4%. A comparative assessment of prognostic value revealed a higher sensitivity of the self-sampling method (100%) compared with the medical fence of the material (66.7%). High specificity of both methods of preparation of samples for HPV-test was revealed: 65% for independent and 72% for medical.
The conclusion. The Qvintip device for self-sampling vaginal discharge for the HPV test has a high predictive value and can be recommended as an alternative method for screening cervical cancer.
Key words: human papillomavirus high carcinogenic risk, HPV test, cervix, sampling, Qvintip, prognostic value.
Полный текст
Список литературы
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3. Del Mistro A, Frayle H, Ferro A et al. Efficacy of self-sampling in promoting participation to cervical cancer screening also in subsequent round. Prev Med Rep 2016; 5: 166–68. DOI: 10.1016/j.pmedr.2016.12.017. eCollection 2017
4. Bosch FX, Broker TR, Forman D et al. Comprehensive control of human papillomavirus infections and related diseases. Vaccine 2013; 31 (Suppl. 7): H1–31.
5. Сухих Г.Т., Прилепская В.Н. Профилактика рака шейки матки: руководство для врачей. Изд. 3-е. М.: МЕДпресс-информ, 2012. / Sukhikh G.T., Prilepskaia V.N. Profilaktika raka sheiki matki: rukovodstvo dlia vrachei. Izd. 3-e. M.: MEDpress-inform, 2012. [in Russian]
6. Lorincz A, Castanon A, Wey Wey Lim A, Sasieni P. New Strategies for HPV-based Cervical Screening. Wom Health (Lond Engl) 2013; 9 (5): 10. DOI: 10.2217/whe.13.48 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880859/
7. Deleré Y, Schuster M, Vartazarowa E et al. Cervicovaginal Self-Sampling Is a Reliable Method for Determination of Prevalence of Human Papillomavirus Genotypes in Women Aged 20 to 30 Years. J Clin Microbiol 2011; 49 (10): 3519–22.
8. СDC. Cervical cancer is preventable 2014. http://www.cdc.gov/vitalsigns/cervical-cancer
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10. Белокриницкая Т.Е., Фролова Н.И., Туранова О.В. и др. Самостоятельный vs врачебный забор материала для ВПЧ-теста: результативность и приемлемость у пациенток разных возрастных групп. Доктор Ру. 2017; 7 (136): 8–14. / Belokrinitskaia T.E., Frolova N.I., Turanova O.V. i dr. Samostoiatel'nyi vs vrachebnyi zabor materiala dlia VPCh-testa: rezul'tativnost' i priemlemost' u patsientok raznykh vozrastnykh grupp. Doktor Ru. 2017; 7 (136): 8–14. [in Russian]
11. Shaniqua L, Jeanne MF. Update on prevention and screening of cervical cancer. World J Clin Oncol 2014; 5 (4): 744–52. DOI: 10.5306/wjco.v5.i4.744
12. Кисин В.И. Инфекции, передаваемые половым путем. Протоколы ведения больных. М.: Ньюдиамед, 2014. / Kisin V.I. Infektsii, peredavaemye polovym putem. Protokoly vedeniia bol'nykh. M.: N'iudiamed, 2014. [in Russian]
13. WHO guidance note: comprehensive cervical cancer prevention and control: a healthier future for girls and women. World Health Organization, 2013.
14. Wright TC, Stoler MH, Behrens CM et al. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol 2015;136 (2): 189–97.
15. Katki HA, Kinney WK, Fetterman B et al. Cervical Cancer Risk for 330,000 Women Undergoing Concurrent HPV Testing and Cervical Cytology in Routine Clinical Practice at a Large Managed Care Organization. Lancet Oncol 2011; 12 (7): 663–72.
16. Chen K, Ouyang Y, Hillemanns P, Jentschke M. Excellent analytical and clinical performance of a dry self-sampling device for human papillomavirus detection in an urban Chinese referral population. J Obstet Gynaecol Res 2016; 42 (12): 1839–45. DOI: 10.1111/jog.13132. Epub 2016 Sep 20.
17. Jentschke M, Chen K, Arbyn M et al. Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections. J Clin Virol 2016; 82: 46–50. DOI: 10.1016/j.jcv.2016.06.016. Epub 2016 Jun 28.
18. Bhatla N, Dar L, Patro AR et al. Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries? Cancer Epidemiol 2009; 33 (6): 446–50.
19. Szarewski A, Cadman L, Mallett S et al. Human papillomavirus testing by self-sampling: assessment of accuracy in an unsupervised clinical setting. J Med Screen 2007; 14 (1): 34–42.
2. Comprehensive Cervical Cancer Control. A guide to essential practice Second edition. World Health Organization, 2014.
3. Del Mistro A, Frayle H, Ferro A et al. Efficacy of self-sampling in promoting participation to cervical cancer screening also in subsequent round. Prev Med Rep 2016; 5: 166–68. DOI: 10.1016/j.pmedr.2016.12.017. eCollection 2017
4. Bosch FX, Broker TR, Forman D et al. Comprehensive control of human papillomavirus infections and related diseases. Vaccine 2013; 31 (Suppl. 7): H1–31.
5. Sukhikh G.T., Prilepskaia V.N. Profilaktika raka sheiki matki: rukovodstvo dlia vrachei. Izd. 3-e. M.: MEDpress-inform, 2012. [in Russian]
6. Lorincz A, Castanon A, Wey Wey Lim A, Sasieni P. New Strategies for HPV-based Cervical Screening. Wom Health (Lond Engl) 2013; 9 (5): 10. DOI: 10.2217/whe.13.48 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880859/
7. Deleré Y, Schuster M, Vartazarowa E et al. Cervicovaginal Self-Sampling Is a Reliable Method for Determination of Prevalence of Human Papillomavirus Genotypes in Women Aged 20 to 30 Years. J Clin Microbiol 2011; 49 (10): 3519–22.
8. СDC. Cervical cancer is preventable 2014. http://www.cdc.gov/vitalsigns/cervical-cancer
9. Rogovskaia S.I. Prakticheskaia kol'poskopiia. Izd. 4-e. M.: GEOTAR-Media, 2016. [in Russian]
10. Belokrinitskaia T.E., Frolova N.I., Turanova O.V. i dr. Samostoiatel'nyi vs vrachebnyi zabor materiala dlia VPCh-testa: rezul'tativnost' i priemlemost' u patsientok raznykh vozrastnykh grupp. Doktor Ru. 2017; 7 (136): 8–14. [in Russian]
11. Shaniqua L, Jeanne MF. Update on prevention and screening of cervical cancer. World J Clin Oncol 2014; 5 (4): 744–52. DOI: 10.5306/wjco.v5.i4.744
12. Kisin V.I. Infektsii, peredavaemye polovym putem. Protokoly vedeniia bol'nykh. M.: N'iudiamed, 2014. [in Russian]
13. WHO guidance note: comprehensive cervical cancer prevention and control: a healthier future for girls and women. World Health Organization, 2013.
14. Wright TC, Stoler MH, Behrens CM et al. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol 2015;136 (2): 189–97.
15. Katki HA, Kinney WK, Fetterman B et al. Cervical Cancer Risk for 330,000 Women Undergoing Concurrent HPV Testing and Cervical Cytology in Routine Clinical Practice at a Large Managed Care Organization. Lancet Oncol 2011; 12 (7): 663–72.
16. Chen K, Ouyang Y, Hillemanns P, Jentschke M. Excellent analytical and clinical performance of a dry self-sampling device for human papillomavirus detection in an urban Chinese referral population. J Obstet Gynaecol Res 2016; 42 (12): 1839–45. DOI: 10.1111/jog.13132. Epub 2016 Sep 20.
17. Jentschke M, Chen K, Arbyn M et al. Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections. J Clin Virol 2016; 82: 46–50. DOI: 10.1016/j.jcv.2016.06.016. Epub 2016 Jun 28.
18. Bhatla N, Dar L, Patro AR et al. Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries? Cancer Epidemiol 2009; 33 (6): 446–50.
19. Szarewski A, Cadman L, Mallett S et al. Human papillomavirus testing by self-sampling: assessment of accuracy in an unsupervised clinical setting. J Med Screen 2007; 14 (1): 34–42.
2. Comprehensive Cervical Cancer Control. A guide to essential practice Second edition. World Health Organization, 2014.
3. Del Mistro A, Frayle H, Ferro A et al. Efficacy of self-sampling in promoting participation to cervical cancer screening also in subsequent round. Prev Med Rep 2016; 5: 166–68. DOI: 10.1016/j.pmedr.2016.12.017. eCollection 2017
4. Bosch FX, Broker TR, Forman D et al. Comprehensive control of human papillomavirus infections and related diseases. Vaccine 2013; 31 (Suppl. 7): H1–31.
5. Сухих Г.Т., Прилепская В.Н. Профилактика рака шейки матки: руководство для врачей. Изд. 3-е. М.: МЕДпресс-информ, 2012. / Sukhikh G.T., Prilepskaia V.N. Profilaktika raka sheiki matki: rukovodstvo dlia vrachei. Izd. 3-e. M.: MEDpress-inform, 2012. [in Russian]
6. Lorincz A, Castanon A, Wey Wey Lim A, Sasieni P. New Strategies for HPV-based Cervical Screening. Wom Health (Lond Engl) 2013; 9 (5): 10. DOI: 10.2217/whe.13.48 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880859/
7. Deleré Y, Schuster M, Vartazarowa E et al. Cervicovaginal Self-Sampling Is a Reliable Method for Determination of Prevalence of Human Papillomavirus Genotypes in Women Aged 20 to 30 Years. J Clin Microbiol 2011; 49 (10): 3519–22.
8. СDC. Cervical cancer is preventable 2014. http://www.cdc.gov/vitalsigns/cervical-cancer
9. Роговская С.И. Практическая кольпоскопия. Изд. 4-е. М.: ГЭОТАР-Медиа, 2016. / Rogovskaia S.I. Prakticheskaia kol'poskopiia. Izd. 4-e. M.: GEOTAR-Media, 2016. [in Russian]
10. Белокриницкая Т.Е., Фролова Н.И., Туранова О.В. и др. Самостоятельный vs врачебный забор материала для ВПЧ-теста: результативность и приемлемость у пациенток разных возрастных групп. Доктор Ру. 2017; 7 (136): 8–14. / Belokrinitskaia T.E., Frolova N.I., Turanova O.V. i dr. Samostoiatel'nyi vs vrachebnyi zabor materiala dlia VPCh-testa: rezul'tativnost' i priemlemost' u patsientok raznykh vozrastnykh grupp. Doktor Ru. 2017; 7 (136): 8–14. [in Russian]
11. Shaniqua L, Jeanne MF. Update on prevention and screening of cervical cancer. World J Clin Oncol 2014; 5 (4): 744–52. DOI: 10.5306/wjco.v5.i4.744
12. Кисин В.И. Инфекции, передаваемые половым путем. Протоколы ведения больных. М.: Ньюдиамед, 2014. / Kisin V.I. Infektsii, peredavaemye polovym putem. Protokoly vedeniia bol'nykh. M.: N'iudiamed, 2014. [in Russian]
13. WHO guidance note: comprehensive cervical cancer prevention and control: a healthier future for girls and women. World Health Organization, 2013.
14. Wright TC, Stoler MH, Behrens CM et al. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol 2015;136 (2): 189–97.
15. Katki HA, Kinney WK, Fetterman B et al. Cervical Cancer Risk for 330,000 Women Undergoing Concurrent HPV Testing and Cervical Cytology in Routine Clinical Practice at a Large Managed Care Organization. Lancet Oncol 2011; 12 (7): 663–72.
16. Chen K, Ouyang Y, Hillemanns P, Jentschke M. Excellent analytical and clinical performance of a dry self-sampling device for human papillomavirus detection in an urban Chinese referral population. J Obstet Gynaecol Res 2016; 42 (12): 1839–45. DOI: 10.1111/jog.13132. Epub 2016 Sep 20.
17. Jentschke M, Chen K, Arbyn M et al. Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections. J Clin Virol 2016; 82: 46–50. DOI: 10.1016/j.jcv.2016.06.016. Epub 2016 Jun 28.
18. Bhatla N, Dar L, Patro AR et al. Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries? Cancer Epidemiol 2009; 33 (6): 446–50.
19. Szarewski A, Cadman L, Mallett S et al. Human papillomavirus testing by self-sampling: assessment of accuracy in an unsupervised clinical setting. J Med Screen 2007; 14 (1): 34–42.
________________________________________________
2. Comprehensive Cervical Cancer Control. A guide to essential practice Second edition. World Health Organization, 2014.
3. Del Mistro A, Frayle H, Ferro A et al. Efficacy of self-sampling in promoting participation to cervical cancer screening also in subsequent round. Prev Med Rep 2016; 5: 166–68. DOI: 10.1016/j.pmedr.2016.12.017. eCollection 2017
4. Bosch FX, Broker TR, Forman D et al. Comprehensive control of human papillomavirus infections and related diseases. Vaccine 2013; 31 (Suppl. 7): H1–31.
5. Sukhikh G.T., Prilepskaia V.N. Profilaktika raka sheiki matki: rukovodstvo dlia vrachei. Izd. 3-e. M.: MEDpress-inform, 2012. [in Russian]
6. Lorincz A, Castanon A, Wey Wey Lim A, Sasieni P. New Strategies for HPV-based Cervical Screening. Wom Health (Lond Engl) 2013; 9 (5): 10. DOI: 10.2217/whe.13.48 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880859/
7. Deleré Y, Schuster M, Vartazarowa E et al. Cervicovaginal Self-Sampling Is a Reliable Method for Determination of Prevalence of Human Papillomavirus Genotypes in Women Aged 20 to 30 Years. J Clin Microbiol 2011; 49 (10): 3519–22.
8. СDC. Cervical cancer is preventable 2014. http://www.cdc.gov/vitalsigns/cervical-cancer
9. Rogovskaia S.I. Prakticheskaia kol'poskopiia. Izd. 4-e. M.: GEOTAR-Media, 2016. [in Russian]
10. Belokrinitskaia T.E., Frolova N.I., Turanova O.V. i dr. Samostoiatel'nyi vs vrachebnyi zabor materiala dlia VPCh-testa: rezul'tativnost' i priemlemost' u patsientok raznykh vozrastnykh grupp. Doktor Ru. 2017; 7 (136): 8–14. [in Russian]
11. Shaniqua L, Jeanne MF. Update on prevention and screening of cervical cancer. World J Clin Oncol 2014; 5 (4): 744–52. DOI: 10.5306/wjco.v5.i4.744
12. Kisin V.I. Infektsii, peredavaemye polovym putem. Protokoly vedeniia bol'nykh. M.: N'iudiamed, 2014. [in Russian]
13. WHO guidance note: comprehensive cervical cancer prevention and control: a healthier future for girls and women. World Health Organization, 2013.
14. Wright TC, Stoler MH, Behrens CM et al. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol 2015;136 (2): 189–97.
15. Katki HA, Kinney WK, Fetterman B et al. Cervical Cancer Risk for 330,000 Women Undergoing Concurrent HPV Testing and Cervical Cytology in Routine Clinical Practice at a Large Managed Care Organization. Lancet Oncol 2011; 12 (7): 663–72.
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Авторы
Т.Е.Белокриницкая*, О.В.Туранова, Н.И.Фролова
ФГБОУ ВО «Читинская государственная медицинская академия» Минздрава России. 672000, Россия, Чита, ул. Горького, д. 39а
*tanbell24@mail.ru
Chita State Medical Academy of the Ministry of Health of the Russian Federation. 672000, Russian Federation, Chita, ul. Gor'kogo, d. 39a
*tanbell24@mail.ru
ФГБОУ ВО «Читинская государственная медицинская академия» Минздрава России. 672000, Россия, Чита, ул. Горького, д. 39а
*tanbell24@mail.ru
________________________________________________
Chita State Medical Academy of the Ministry of Health of the Russian Federation. 672000, Russian Federation, Chita, ul. Gor'kogo, d. 39a
*tanbell24@mail.ru
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